Compensated and Decompensated Stages of Cirrhosis - Viral Hepatitis and Liver Disease
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Compensated and Decompensated Stages of Cirrhosis

for Health Care Providers

Management of Complications: Quicknotes - Cirrhosis

The Cirrhosis Quicknotes provide bottom-line current recommendations regarding management of compensated and decompensated cirrhosis, including guidelines for screening and management of varices and hepatocellular carcinoma (HCC) and guidelines for the management of variceal hemorrhage, spontaneous bacterial peritonitis, ascites, hepatorenal syndrome, and encephalopathy, including dosages of recommended medications and goals of therapy. They also provide guidance regarding referral for liver transplantation.

The Cirrhosis Quicknotes are based on 2016 Practice Guidance by the American Association for the Study of Liver Diseases Guidelines on Portal Hypertensive Bleeding in CirrhosisLink will take you outside the VA website. VA is not responsible for the content of the linked site. and the 2009 recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program on the Management and Treatment of Patients with Cirrhosis and Portal Hypertension.Link will take you outside the VA website.

I. Management of Compensated Cirrhosis

No ascites, variceal hemorrhage, encephalopathy, or jaundice

HCC surveillance (every 6 months)

  • Ultrasound
  • AFP

Varices surveillance (upper endoscopy)

In HCV cirrhosis: if liver stiffness <20 kPa and platelet count >150,000, could forego endoscopy (low likelihood of medium/large varices)

Repeat endoscopy in 3 years if etiology removed OR in 2 years if ongoing injury OR at the time of decompensation

Nonselective beta-blockers (propranolol or nadolol) or carvedilol

  • Propranolol (20-160 mg BID) or nadolol (20-160 mg QD); titrate to maximum tolerable dosage or a heart rate of 55-60 beats/min
  • Carvedilol, maximum 12.5 mg/day
  • No need to repeat endoscopy
  • Nonselective beta-blockers optional
  • If NO beta-blockers given, repeat endoscopy: in 2 years if etiology removed OR in 1 year if ongoing injury OR at the time of decompensation

Nonselective beta-blockers (propranolol, nadolol) or Carvedilol

  • Propranolol (20-160 mg BID) or nadolol (40-160 mg QD); titrate to maximum tolerable dosage or a heart rate of 55-60 beats/min
  • Or carvedilol at maximum dose of 12.5 mg/day
  • No need to repeat endoscopy

OR

Endoscopic variceal ligation (choice depends on patient characteristics and preferences, local resources)

  • Ligate every 1-2 weeks until variceal obliteration
  • First surveillance endoscopy 1-3 months after obliteration, then every 6-12 months indefinitely

II. Management of Decompensated Cirrhosis

Patient has developed ascites, variceal hemorrhage, or encephalopathy

HCC surveillance (every 6 months)

  • Ultrasound
  • AFP

Varices surveillance (upper endoscopy) in a patient with decompensated cirrhosis and NO prior variceal hemorrhage

Repeat endoscopy every year

Nonselective beta-blockers (propranolol or nadolol) but not carvedilol

  • Propranolol (20-160 mg BID) or nadolol (20-160 mg QD)
  • In patients with ascites cap dose to 80 mg (BID for propranolol, QD for nadolol)
  • Titrate to maximum tolerable dosage or a heart rate of 55-60 beats/min
  • No need to repeat endoscopy

OR

Endoscopic variceal ligation

  • Ligate every 1-2 weeks until variceal obliteration
  • First surveillance endoscopy 1-3 months after obliteration, then every 6-12 months
  • Nonselective beta-blockers optional, doses as above
  • If no beta-blockers given, repeat endoscopy in 1 year

Nonselective beta-blockers (propranolol, nadolol) but not carvedilol

  • Propranolol (20-160 mg BID) or nadolol (20-160 mg QD)
  • In patients with ascites cap dose to 80 mg (BID for propranolol, QD for nadolol)
  • Titrate to maximum tolerable dosage or a heart rate of 55-60 beats/minute
  • No need to repeat endoscopy

OR

Endoscopic variceal ligation

  • Ligate every 1-2 weeks until variceal obliteration
  • First surveillance endoscopy 1-3 months after obliteration, then every 6-12 months

Variceal hemorrhage (if no history, follow guidelines for varices surveillance in compensated cirrhosis)

Any of the following findings on upper endoscopy performed within 12 hours from admission:

  • Active bleeding from a varix
  • Stigmata of variceal hemorrhage (white nipple sign)
  • Presence of gastroesophageal varices without another source of hemorrhage
  • Establish Child-Pugh score on admission
  • Cautious transfusion of fluids and PRBC with a goal hemoglobin of ~7-8 g/dL
  • Antibiotic prophylaxis (3-7 days) with:
    • Ceftriaxone 1 g/day (IV)
  • Pharmacologic therapy initiated as soon as diagnosis is suspected
    • Octreotide 50 mcg IV bolus followed by continuous infusion 50 mcg/hour (3-5 days)
  • Endoscopy within 12 hours of admission with ligation performed if variceal source is confirmed
  • In patients with CPS of 10-13, placement of TIPS must be considered within 24-48 hours of endoscopy (early TIPS)

Considered in patients with bleeding esophageal varices who are not candidates for early TIPS and who have failed pharmacologic + endoscopic therapy or in patients with bleeding gastric fundal varices who have failed one endoscopic therapy (cyanoacrylate)

Nonselective beta-blockers (propranolol, nadolol) but not carvedilol

  • Propranolol (20-160 mg BID) or nadolol (20-160 mg QD)
  • In patients with ascites cap dose to 80 mg (BID for propranolol, QD for nadolol)
  • Titrate to maximum tolerable dosage or a heart rate of 55-60 beats/min

AND

Endoscopic variceal ligation

  • Ligate every1-2 weeks until variceal obliteration
  • First surveillance endoscopy 1-3 months after obliteration, then every 6-12 months
  • TIPS if patient rebleeds on combined NSBB + ligation
  • Consider TIPS if patient bled while on NSBB or in patients who cannot tolerate NSBB (ligation alone is suboptimal tx)
  • Once TIPS is successfully placed, there is no need for NSBB or ligation

Spontaneous bacterial peritonitis (SBP)

Consider SBP and perform diagnostic paracentesis if:

  • Symptoms/signs (abdominal pain, fever, chills)
  • Patient is in ER or admitted
  • Worsening renal function or encephalopathy

SBP present if ascites PMN count >250 cells/ µL (if fluid macroscopically bloody, subtract 1 PMN per 250 RBC/ µL)

  • Avoid large-volume paracenteses during active infection
  • Intravenous albumin (1 g/kg of body weight) if BUN >30 mg/dL, creatinine >1 mg/dL, bilirubin >4 mg/dL; repeat at day 3 if renal dysfunction persists
  • Avoid aminoglycosides
  • Cefotaxime 2 g IV every 12 hours OR
  • Ceftriaxone 2 g every 24 hours
  • Ceftazidime 2 g every 8 hours

Broader-spectrum antibiotics:

  • Vancomycin + Zosyn or
  • Meropenem + daptomycin
  • Continue therapy for 7 days
  • Repeat diagnostic paracentesis at day 2:
    • If ascites PMN count decreases by at least 25% at day 2, IV therapy can be narrowed (if started on broad spectrum AB and organism susceptible) to complete 7 days of therapy
    • If ascites PMN has not decreased or increases, image the abdomen (at least flat film to detect free air), check culture results and consider broadening antibiotic spectrum
  • Oral ciprofloxacin 500 mg QD OR
  • Oral levofloxacin 250 mg QD

TMP-SMX 1 double-strength tablet PO QD (Patients who develop quinolone-resistant organisms may also have resistance to TMP-SMX)

Prophylaxis should be continued until the disappearance of ascites, time of transplantation, or death

Ascites

  • Treat ascites once other complications have been treated
  • Avoid NSAIDs
  • 1-2 g/day
  • Liberalize if restriction results in poor food intake

Spironolactone based:

  • Spironolactone alone (start at 50-100 mg QD, single morning dose) OR
  • Spironolactone (50-100 mg QD) + furosemide (start at 20-40 mg QD, single morning dose)

Use as initial therapy only in patients with tense ascites; give IV albumin (6-8 g/L of ascites removed)

  • Adjustment of diuretic dosage should be performed every 4-7 days
  • Patient should be weighed at least weekly and BUN, creatinine, and electrolytes measured every 1-2 weeks while adjusting dosage
  • Double dosage of diuretics if:
    • Weight loss <2 kg (4 lb) a week AND
    • BUN, creatinine, and electrolytes OK
  • Halve dosage of diuretics or discontinue if:
    • Weight loss ≥0.5 kg (1 lb)/ day OR
    • Abnormalities in BUN, creatinine, or electrolytes
  • Maximum diuretic dosage is spironolactone (400 mg QD) and furosemide (160 mg QD)
  • Ascites that is not eliminated even with maximum diuretic therapy
  • Ascites that is not eliminated because maximum dosages of diuretics cannot be attained given the development of diuretic-induced complications
  • Total paracentesis + IV albumin (6-8 g/L of ascites removed)
  • If <5 L of ascites is removed, a synthetic plasma volume expander may be used instead of albumin
  • Continue with salt restriction and diuretic therapy as tolerated
  • TIPS in patients with MELD <15 (think of it sooner rather than later); once TIPS is successfully placed, NSBB for prevention of variceal hemorrhage can be discontinued
  • Peritoneovenous shunt for patients who are not TIPS or transplant candidates

Hepatorenal syndrome (HRS)

  • Diagnosis of AKI: increase in serum creatinine by ≥ 0.3 mg/dL or ≥1.5 X from baseline
  • Main differential is between prerenal azotemia (most common), ATN and HRS (least common)
  • PRA and HRS are prerenal (functional) forms of AKI and should be suspected with FeNa <0.5% ( <0.1% suggests HRS), evidence of volume depletion (overdiuresis, diarrhea, GI bleed), factors that will worsen vasodilatation (infection, vasodilators) or use of NSAIDs
  • ATN is an intrarenal (structural) from of AKI and should be suspected with FeNA >0.5%, if there is clinical evidence of severe hypoperfusion (shock), history of nephrotoxins or contrast dye, casts in urine, albuminuria >100 mg/dL (in the absence of CKD)
  • Panculture, diagnostic paracentesis, start antibiotics if strong suspicion of infection (SIRS)
  • Discontinue diuretics, vasodilators, NSAIDs, nonselective beta-blockers
  • If GI bleed or diarrhea, treat accordingly
  • Expand with saline (if obvious dehydration)
  • IV albumin 25-50 g BID if creatinine increases despite general measures outlined above
  • If creatinine continues to increase despite all above measures and albumin infusion and, after excluding ATN or other structural causes of AKI, start specific therapy for HRS
  • A patient with HRS typically has ascites (refractory), hyponatremia, low MAP and a FeNa <0.1%

Vasoconstrictors

  • Octreotide (100-200 mcg SC TID) PLUS Midodrine (7.5-12.5 mg PO TID)
  • Norepinephrine (0.02 to 0.4 mcg/kg/min)
  • Terlipressin (0.5-2.0 mg IV every 4-6 hours)

Goal to increase MAP by 10 to 15 mmHg

AND

IV albumin (50-100 g IV QD)

Both for at least 7 days

Sequence of therapy

In the absence of terlipressin (preferred):

  • Start octreotide+midodrine on floor but advance doses quickly based on effect on MAP, creatinine/urine output
  • If no effect in any of these parameters at day 3 of therapy with octreotide/midodrine → transfer to ICU for norepinephrine infusion

Hepatic encephalopathy (HE)

  • Identify and treat precipitating factor (GI hemorrhage, infection, prerenal azotemia, constipation, sedatives)
  • Do not assume that HE is the result of noncompliance to lactulose before ruling out precipitants
  • Lactulose enemas (300 cc in 1 liter of water) in patients who are unable to take it PO
  • Lactulose 25 mL PO every 1-2 hours until at least two soft or loose BM are produced and then adjust to 2-3 BM/day
  • Lactulose can be discontinued once precipitating factor has resolved
  • In an otherwise compensated patient in whom there is no precipitant, look for a spontaneous splenorenal shunt that could then be embolized
  • No long-term protein restriction
  • Protein from dairy or vegetable sources is preferable to animal protein
  • Avoid sedatives and tranquilizers
  • Avoid constipation

Lactulose dosage that produces 2-3 soft, formed bowel movements per day, starting at 15-30 cc PO BID

  • Rifaximin 550 mg PO BID in patients who cannot tolerate lactulose
  • Rifaximin + lactulose in patients with recurrent or persistent HE
  • In patients with TIPS and recurrent HE, consider TIPS reduction; if TIPS is reduced and patient needs prophylaxis for variceal hemorrhage, NSBB should be restarted
  • In patients without TIPS and recurrent HE, look for a spontaneous splenorenal shunt that could be embolized

When to refer for transplant evaluation

Calculate:

  • CTP score ( calculator)
    • Prepare transplant evaluation packet if CTP score ≥7
  • MELDNa score ( calculator)
    • Prepare transplant evaluation packet if:
      • MELDNa score ≥15
      • HCC criteria met (1 tumor ≥2 cm; or no more than 3 tumors ≤ 3 cm; or no more than 1 tumor ≤ 5 cm; downstaging per regional review board)

Frequency of follow-up visits

Depends on MELDNa score ( calculator)

  • ≤10: every 6-12 months
  • 11-18: every 3 months
  • 19-24: every month
  • ≥25: every week